Dynamics and stochastic resonance in a mathematical model of bistable phosphorylation and nuclear size control

Abstract

Robust oscillations play crucial roles in a wide variety of biological processes and are often generated by deterministic mechanisms. However, stochastic fluctuations often generate complex perturbations of these deterministic oscillations, potentially strengthening or weakening their robustness. In this paper, we study bistable phosphorylation as a mechanism for robust oscillation. We present a simple nucleocytoplasmic transport and cell growth model where cargo proteins undergo bistable phosphorylation prior to nuclear import. We perform a detailed bifurcation analysis to examine the system's dynamical behavior. We then introduce additive noise into the model and study the stochastic resonance behavior and robustness of oscillations under noise. Our results show that, depending on the phosphorylation threshold, time-scale parameters, and nucleocytoplasmic transport rate, bistable phosphorylation may generate oscillations via Hopf bifurcations; moreover, stochastic resonance and Bautin bifurcations enhance the robustness of the oscillations.